Urinary infections constitute a fairly serious medical problem in the United States and the developed world. Approximately 1-5% of the population of the United States is documented to suffer from recurrent urinary tract infection. Approximately 0.1% of these cases encounter the complication of pyelonephritis. Substantially larger numbers of the population, while not afflicted with recurrent infection, are at potential risk to serious complications, even with one episode of pyelonephritis because of an underlying medical condition. Persons at risk include those who have diabetes mellitus (approximately 10 million in the United States), the elderly, persons with renal insufficiency, users of excessive quantities of analgesics, and persons whose immune systems are suppressed e.g., patients being treated with chemotherapy for neoplasms. All of these individuals are at risk for serious complications, permanent disability, and even death from urinary tract infections.
It would be helpful to provide an effective vaccine which would protect the relevant members of the population from urinary tract infection. Not only would this prevent the suffering and debilitation now occasioned by the onset of actual infection, it also obviates the need for administration of antibiotics which would be required to treat it. Such avoidance lessens the selective pressure on the infectious biomass caused by excessive use of antibiotics, and delays the appearance of resistant strains.
Because the target infections are not usually regarded as imminent life-threatening risks, it is necessary to provide a vaccine which itself offers little or no risk. Materials which have been available heretofore as active ingredients of such vaccines are limited to microorganisms having attenuated pathogenicity and to impure protein preparations which are likely to elicit unwanted immunogenic responses and/or result in undesirable side effects. U.S. Ser. No. 605,287, filed Apr. 30, 1984 discloses a vaccine which is a chemically defined protein comprising particular sequences within HU849 pilin (see below), which is, therefore, noninfectious, and elicits specific antibodies against the organelles of E. coli uropathogens responsible for the colonization of the urinary tract, considered the first step in infection. The present invention adds to the repertoire of available immunogens with these advantages, and as an additional benefit, provides a means for eliciting protective action from even very short, easily synthesized sequences.